System and method for phototherapy for preventing or treating carbon monoxide poisoning

ABSTRACT

Systems and methods are provided for treating or preventing carbon monoxide poisoning. In particular, systems and methods are provided for a phototherapy treatment or prevention system that delivers light radiation to a patient&#39;s body to photodissociate carbon monoxide from hemoglobin.

CROSS-REFERENCES TO RELATED APPLICATIONS

This patent application is a division of U.S. patent application Ser.No. 15/575,000, filed on Nov. 17, 2017, which is a United StatesNational Phase entry of PCT Application No. PCT/US2016/032845, filed onMay 17, 2016, which is based on and claims priority to U.S. ProvisionalPatent Application No. 62/163,277, filed May 18, 2015, which are allincorporated by reference in their entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

Not Applicable.

BACKGROUND

Carbon monoxide (CO) poisoning impairs tissue oxygenation as CO avidlybinds to hemoglobin (Hb) to form carboxyhemoglobin (COHb), which cannottransport oxygen. Currently, treatment of CO poisoning involvesbreathing 100% oxygen to attempt to rapidly remove CO. Hyperbaric oxygentherapy and/or hyperventilation therapy or exercise can further increasethe rate of CO elimination but the necessary facilities and equipmentmay be not be readily available. Visible light is also known tophotodissociate CO from Hb, with a single photon dissociating one COmolecule from Hb.

Smyczynski suggested in Unites States Patent Application Publication No.2013/0101464 that light radiation at 540 nanometers (nm) and/or 570 nmcould be used to treat CO poisoning by photodissociating COHb in bloodpassing through an extracorporeal gas exchanger. The treatment system ofSmyczynski involves removing and recirculating anticoagulated blood froma patient through an extracorporeal oxygenator. The blood passingthrough the extracorporeal oxygenator is irradiated with light at either540 nm and/or 570 nm. The extracorporeal oxygenator is designed suchthat the blood-light contact surface is as large as possible because the540 nm and/or 570 nm light does not penetrate deeply into the bloodstream before becoming completely absorbed.

The 540 nm and 570 nm light wavelengths are chosen by Smyczynski becausethese wavelengths align with peaks in the COHb absorption spectra.However, light at 540 nm and 570 nm are poorly transmitted through humantissue, which requires the treatment system of Smyczynski to remove theblood from the patient's body to perform the phototherapy.

BRIEF SUMMARY

The present disclosure provides systems and methods for treating orpreventing carbon monoxide poisoning. In particular, systems and methodsare provided for a phototherapy treatment or prevention system thatdelivers light radiation to a patient's body to photodissociate carbonmonoxide from hemoglobin. The CO that is removed from the blood isdelivered to the alveoli of the lung or the air or other gasessurrounding the skin for removal from the body.

In one aspect, the present disclosure provides a phototherapy system fortreating or controlling an amount of carbon monoxide poisoning in apatient including a light source configured to output light. The lightoutput from the light source having properties to enablephotodissociation of carboxyhemoglobin in the patient. The phototherapysystem further including an optical cable coupled to the light sourceand having one or more waveguides arranged within the optical cable. Theone or more waveguides are configured to emit light from the lightsource directly on a portion of the patient's body to photodissociatecarboxyhemoglobin.

In another aspect, the present disclosure provides a phototherapy systemfor treating or controlling an amount of carbon monoxide poisoning in apatient including a tube having a central lumen, a bag attached to adistal end of the tube, and a light source configured to be fluidlycommunicated into the bag via the central lumen to emit light into thebag. The light emitted by the light source having properties to enablephotodissociation of carboxyhemoglobin in the patient. The tube and bagare configured to be inserted into or placed onto a portion of thepatient's body to deliver the light emitted through the bag onto theportion of the patient's body to photodissociate carboxyhemoglobin.

In yet another aspect, the present disclosure provides a phototherapysystem for treating or controlling an amount of carbon monoxidepoisoning in a patient including a light source in communication with anaerosolizing element, and a tube configured to provide communicationbetween the light source and an airway. The airway configured to providecommunication to at least one of a nose and a mouth of the patient. Theaerosolizing element is configured to aerosolize the light source todeliver the light source to the patient by ventilation of gas throughthe airway.

In still another aspect, the present disclosure provides a method fortreating or preventing carbon monoxide poisoning in a patient includingproviding a light source, positioning the light source adjacent to orwithin a portion of the patient's body, and emitting light from thelight source directly onto the portions of the patient's body.

The foregoing and other aspects and advantages of the invention willappear from the following description. In the description, reference ismade to the accompanying drawings which form a part hereof, and in whichthere is shown by way of illustration a preferred embodiment of theinvention. Such embodiment does not necessarily represent the full scopeof the invention, however, and reference is made therefore to the claimsand herein for interpreting the scope of the invention.

BRIEF DESCRIPTION OF DRAWINGS

The invention will be better understood and features, aspects andadvantages other than those set forth above will become apparent whenconsideration is given to the following detailed description thereof.Such detailed description makes reference to the following drawingswhich may not be drawn to scale.

FIG. 1 shows a phototherapy system in accordance with one embodiment ofthe present disclosure.

FIG. 2 shown is a cross-sectional view of an optical cable of thephototherapy system of FIG. 1 taken along line 2-2.

FIG. 3 shows a tip defining a substantially conical shape in accordancewith one embodiment of the present disclosure.

FIG. 4 shows a tip defining a substantially round shape in accordancewith another embodiment of the present disclosure.

FIG. 5 shows a tip including one or more diffusing elements inaccordance with yet another embodiment of the present disclosure.

FIG. 6 shows an optical cable of the phototherapy system of FIG. 1inserted into an esophagus of a patient.

FIG. 7 shows an optical cable of the phototherapy system of FIG. 1inserted into a right mainstem bronchus of a patient.

FIG. 8 shows waveguides of the phototherapy system of FIG. 1 displacedthroughout the bronchial tree of a patient.

FIG. 9 shows a tip including a fin to control a drag force across thetip in accordance with another embodiment of the present disclosure.

FIG. 10. shows the phototherapy system of FIG. 1 where a distal end ofan optical cable is split into a first distal section and a seconddistal section.

FIG. 11 shows waveguides of the phototherapy system of FIG. 10 displacedthroughout the bronchial tree of a patient.

FIG. 12 shows the phototherapy system of FIG. 1 including a balloon, aliquid source, and a gas source.

FIG. 13 shows the phototherapy system of FIG. 12 where the balloon is inan inflated state.

FIG. 14 shows an optical cable of the phototherapy system of FIG. 13inserted into an esophagus of a patient.

FIG. 15 shows the phototherapy system of FIG. 1 integrated with abronchoscope in accordance with one embodiment of the presentdisclosure.

FIG. 16 outlines the steps for operating the phototherapy system of FIG.1 in accordance with one embodiment of the present disclosure.

FIG. 17 shows a phototherapy system in accordance with anotherembodiment of the present disclosure.

FIG. 18 outlines the steps for operating the phototherapy system of FIG.17 in accordance with one embodiment of the present disclosure.

FIG. 19 shows a phototherapy system in accordance with yet anotherembodiment of the present disclosure.

FIG. 20 outlines the steps for operating the phototherapy system of FIG.19 in accordance with one embodiment of the present disclosure.

FIG. 21A shows inhaled or exhaled carbon monoxide concentration versustime for a murine model of carbon monoxide poisoning.

FIG. 21B shows carboxyhemoglobin percentage versus time for a murinemodel of carbon monoxide poisoning.

FIG. 22 shows a phototherapy system applying laser light directly to thelungs of a mouse in accordance with one embodiment of the presentdisclosure.

FIG. 23A shows inhaled or exhaled carbon monoxide concentration versustime during phototherapy on mice breathing either air or 100% oxygenpoisoned with 400 ppm CO for one hour.

FIG. 23B shows carboxyhemoglobin percentage versus time duringphototherapy on mice breathing 100% oxygen poisoned with 400 ppm CO forone hour.

FIG. 23C shows inhaled or exhaled carbon monoxide concentration versustime during phototherapy on mice breathing air poisoned with 400 ppm COfor one hour.

FIG. 23D shows carboxyhemoglobin percentage versus time duringphototherapy on mice breathing air poisoned with 400 ppm CO for onehour.

FIG. 24A shows systolic arterial pressure versus time for mice with andwithout phototherapy at 628 nm.

FIG. 24B shows heart rate versus time for mice with and withoutphototherapy at 628 nm.

FIG. 25 shows the effect of phototherapy at 628 nm on mice body and lungtemperature.

FIG. 26A shows the effect of wavelength on the time to eliminate 90%carbon monoxide.

FIG. 26B shows carboxyhemoglobin half-life versus irradiance at 628 nm.

FIG. 26C shows the effect of pulse duration and irradiance on the timeto eliminate 90% carbon monoxide.

FIG. 26D shows time to eliminate 90% carbon monoxide versus radiantexposure at 532 nm.

FIG. 27A shows inhaled and exhaled carbon monoxide concentrations versustime for mice with or without simultaneous phototherapy.

FIG. 27B shows cumulative carbon monoxide uptake versus time for micewith or without simultaneous phototherapy.

FIG. 27C shows carboxyhemoglobin percentage versus time for mice with orwithout simultaneous phototherapy.

FIG. 28A shows survival rate versus time for mice with and withoutphototherapy at 532 nm.

FIG. 28B shows carboxyhemoglobin percentage versus time for mince withand without phototherapy at 532 nm.

FIG. 28C shows systolic arterial pressure versus time for mice with andwithout phototherapy at 532 nm.

FIG. 28D shows heart rate versus time for mice with and withoutphototherapy at 532 nm.

FIG. 28E shows blood lactate level versus time for mice with and withoutphototherapy at 532 nm.

FIG. 29A shows a CT scan of a mouse with an optical fiber placed in theesophagus of the mice.

FIG. 29B shows inhaled or exhaled carbon monoxide concentration versustime for mice breathing 100% oxygen with and without esophagealphototherapy.

FIG. 29C shows carboxyhemoglobin percentage versus time for micebreathing 100% oxygen with and without esophageal phototherapy.

FIG. 30A shows inhaled or exhaled carbon monoxide concentration versustime during phototherapy of rats breathing either air or 100% oxygenpoisoned with 500 ppm CO for 90 minutes.

FIG. 30B shows carboxyhemoglobin percentage as a function of time duringphototherapy of rats breathing either air or 100% oxygen after poisoningwith 500 ppm CO for 90 minutes.

FIG. 31A shows exhaled carbon monoxide concentration as a function oftime with and without phototherapy at 532 nm of rats breathing eitherair or 100% oxygen after poisoning with 500 ppm CO for 90 minutes.

FIG. 31B shows carboxyhemoglobin percentage as a function of time withand without phototherapy at 532 nm of rats breathing either air or 100%oxygen after poisoning with 500 ppm CO for 90 minutes.

FIG. 32A shows mean arterial pressure as a function of time with andwithout phototherapy at 532 nm of rats breathing air after poisoningwith 500 ppm CO for 90 minutes.

FIG. 32B shows heart rate as a function of time with and withoutphototherapy at 532 nm of rats breathing air after poisoning with 500ppm CO for 90 minutes.

FIG. 32C shows carboxyhemoglobin percentage as a function of time withand without phototherapy at 532 nm of rats breathing air after poisoningwith 500 ppm CO for 90 minutes.

FIG. 32D shows lactate levels as a function of time with and withoutphototherapy at 532 nm of rats breathing air after poisoning with 500ppm CO for 90 minutes.

FIG. 33A shows inhaled or exhaled carbon monoxide concentration as afunction of time with or without hyperventilation and phototherapy at532 nm of rats breathing 100% oxygen after poisoning with 500 ppm CO for90 minutes.

FIG. 33B shows carboxyhemoglobin percentage as a function of time withor without hyperventilation and phototherapy at 532 nm of rats breathing100% oxygen after poisoning with 500 ppm CO for 90 minutes.

FIG. 34A shows eliminated carbon monoxide with and without intrapleuralphototherapy at 532 nm of rats breathing 100% oxygen after poisoningwith 500 ppm CO for 90 minutes.

FIG. 34B shows carboxyhemoglobin half-life with and without intrapleuralphototherapy at 532 nm of rats breathing 100% oxygen after poisoningwith 500 ppm CO for 90 minutes.

FIG. 35 shows a light spectrum produced by a chemiluminescence reactionused for chemiluminescence phototherapy.

FIG. 36A shows eliminated carbon monoxide with and withoutchemiluminescence phototherapy at 532 nm of rats breathing 100% oxygenafter poisoning with 500 ppm CO for 90 minutes.

FIG. 36B shows carboxyhemoglobin half-life with and withoutchemiluminescence phototherapy at 532 nm of rats breathing 100% oxygenafter poisoning with 500 ppm CO for 90 minutes.

DETAILED DESCRIPTION

The term “visible light” as used herein refers to a portion of theelectromagnetic spectrum, generally bound between wavelengths ofapproximately 380 nanometers (nm) and approximately 750 nm, that isvisible to the human eye. One of skill in the art would recognize thatthe wavelength range of visible light will vary from person to persondepending on one's vision. Thus, the range from 380 nm to 750 nm is agenerally accepted range and is not meant to be definitively limiting inany way.

Carbon monoxide (CO) poisoning is one of the most common causes ofpoison-related death worldwide. In the United States, CO inhalationcauses approximately 50,000 emergency room visits and more than 400accidental deaths each year. Even when it is not lethal, CO intoxicationis associated with significant morbidity, including memory, attention,and affect disorders.

CO and oxygen have an equal probability of binding to hemoglobin (Hb);however, once bonded, CO binds to Hb with an affinity approximately 200times greater than oxygen. Therefore, it takes much longer to dissociateCO from Hb decreasing the likelihood of oxygen bonding to Hb.

As described above, phototherapy with visible light can be used tophotodissociate COHb. Typically, phototherapy techniques have utilizedlight wavelengths which are highly absorbed by COHb (e.g., 540 nm and570 nm). However, the probability of photodissociating COHb duringphototherapy can be independent of the wavelength of light. That is, aquantum yield defined as a ratio between a chemical yield (how manymolecules are photodissociated from Hb) and how many photons areabsorbed can be independent of the wavelength of light. The CO poisoningtreatment or prevention systems and methods of the present disclosureleverage this non-intuitive phenomenon by utilizing wavelengths of lightthat are poorly absorbed by COHb but can sufficiently penetrate humantissue. In one non-limiting example, these wavelengths of light may bebetween 590 nm and 630 nm.

Utilizing wavelengths of light that can sufficiently penetrate humantissue enable the CO poisoning treatment or prevention systems andmethods of the present disclosure, described in great detail below, toprovide phototherapy directly to one or more portions of a patient'sbody that offer access to a large volume of blood flow. One portion ofthe patient's body of particular interest is the lungs and, inparticular, the pulmonary vasculature. Visible light radiated within thepatient's body could reach the pulmonary vasculature if the radiatedvisible light could sufficiently penetrate the interfering tissue. Thepulmonary vasculature, including arteries, alveolar-capillary networks,and veins, provides access to a large volume of blood flow (the entirecardiac output) that is constantly re-circulating during every breathingcycle due to ventilation-perfusion matching. In a healthy human, theentire blood volume of approximately 5 liters circulates through thelung once each minute. Additionally, the pulmonary vasculature issurrounded by the alveoli where photodissociated CO can be released intothe alveolar gas space and expelled from the patient's body uponexhalation.

Phototherapy with visible light also has the potential tophotodissociate oxyhemoglobin (HbO₂) in the lung, which could hinder thetreatment or prevention of CO poisoning by further impairing tissueoxygenation. However, the quantum yield associated with thephotodissociation of HbO₂ using visible light is approximately 0.008,while the quantum yield associated with the photodissociation of COHbusing visible light is approximately 0.5 or higher. Thus, asignificantly larger portion of the COHb is photodissociated to deoxyHbas compared to the HbO₂ which aids in the restoration of HbO₂ levels inthe blood.

The following detailed description is directed towards variousnon-limiting examples of systems and methods that can providephototherapy to treat or prevent CO poisoning by radiating visible lightinto the pulmonary vasculature or skin.

FIG. 1 illustrates one non-limiting example of a phototherapy system 10for treating or preventing CO poisoning. The phototherapy system 10includes a controller 12 in communication with a light source 14. Thelight source 14 can be in the form of a laser configured to outputvisible light at a wavelength between approximately 590 nm and 650 nm.In other non-limiting examples, the light source 14 may be in the formof a light-emitting-diode (LED), or any other visible light emittingdevice known in the art. The controller 12 is configured to control thepulse width, frequency, and energy output of the light source 14. Thecontroller 12 is also configured to cycle the light source 14 on andoff, and control the duration the light source 14 is turn on, asdesired. Additionally, as shown in FIG. 1, the controller 12 is incommunication with an EKG signal 13 of a patient and an airflow meter15. The airflow meter 15 is configured to measure the flow rate ofoxygen or air through the patient's trachea and bronchial tree andenables the controller 12 to identify when the patient is inhaling andexhaling. Thus, the controller 12 may be configured to gate an opticalsignal supplied to the light source 14 to end inspiration thereby savingpower and reducing heating of lung tissue, and allowingimmediate-subsequent exhalation of CO rich gas. Additionally oralternatively, the controller 12 can be in communication with ameasurement device, for example a transcutaneous COHb pulse oximeter,capable of continuously measuring the arterial CO concentration in apatient's blood. The controller 12 can be configured to turn off thelight source 14 once the CO concentration in the patient's blood hassufficiently reduced.

As described above, peak absorption of visible light by COHb occurs near540 nm and 570 nm. The absorption of visible light by COHb substantiallydecreases as wavelength increases above 570 nm, with little to noabsorption occurring above 690 nm. Although the absorption of visiblelight by COHb substantially decreases above 570 nm, the penetrationdepth of visible light into, or through, human tissue increases aswavelength increases above approximately 570 nm. Thus, the wavelength oflight output by the light source 14 is capable of sufficientlypenetrating into, or through, human tissue and also capable of beingabsorbed by COHb.

In other non-limiting examples, the light source 14 may be configured tooutput light at a wavelength between approximately 380 nm andapproximately 750 nm. In still other non-limiting examples, the lightsource 14 may be configured to output light at any wavelength absorbedby COHb, as desired.

With reference to FIGS. 1 and 2, the light source 14 is coupled to anoptical cable 16 such that the light output from the light source 14 istransmitted through one or more waveguides 18 arranged within and alongthe optical cable 16. The optical cable 16 defines a substantiallycylindrical shape and is dimensioned such that a diameter D of theoptical cable 16 is small enough to ensure a patient can be ventilatedor breathe around the optical cable 16 if inserted into the patient'sesophagus or trachea. In one non-limiting example, the diameter D of theoptical cable 16 can be less than approximately ten millimeters (mm). Inother non-limiting examples, the optical cable 16 may define a differentshape, as desired.

The optical cable 16 may be fabricated from a flexible, biocompatiblematerial capable of bending without deforming while being inserted intothe patient's esophagus or respiratory tract. Alternatively oradditionally, the optical cable 16 can be received within a flexible,biocompatible tube, such as a PVC tube, a PTFE tube, a PES tube, or anyflexible, biocompatible tube known in the art. The optical cable 16 ortube can be part of an endotracheal tube, or an endotracheal tube fittedwith an extra lumen (or double lumen endotracheal tube such as used toobtain lung isolation in thoracic surgery). The waveguides 18 can beplaced separately in each main stem bronchus, or passed beyond, underdirect visualization with a fiber optic bronchoscope.

The waveguides 18 are fabricated from a flexible, biocompatible materialthat is capable of efficiently transmitting the light output by thelight source 14, such as glass, plastic, liquid, gel, or any otherviable material known in the art. In the illustrated non-limitingexample, the waveguides 18 are one or more optical fibers. In anothernon-limiting example, the waveguides 18 can be collagen gel, which, inaddition to being flexible and biocompatible, is also biodegradable. Thewaveguides 18 can each define a waveguide diameter D_(f) and can bedimensioned to be longer than the optical cable 16 such that a portionof the waveguides 18 protrude from a distal end 20 of the optical cable16. The waveguide diameter D_(f) can be between approximately 5micrometers (μm) and 1000 μm. In other non-limiting examples, thewaveguide diameter D_(f) can be less than 5 μm or greater than 1000 μm,as desired.

In the illustrated non-limiting example of FIG. 1, each of thewaveguides 18 protrude an equal distance from distal end 20 of theoptical cable 16. In another non-limiting example, the waveguides 18 caneach protrude a different distance from the distal end 20 of the opticalcable 16. The distance that each waveguide 18 protrudes can be a fixedpredetermined value that is different or the same for each waveguide 18or, in other non-limiting examples, the distance that each waveguide 18protrudes from the optical cable 16 can be variably controlled by a userof the phototherapy system 10. The distal end 20 of the optical cable 16may include a stent-like structure (not shown) that contains the portionof the waveguides 18 that protrude from the optical cable 16. Thestent-like structure can aid in preventing the waveguides 18 fromcontacting tissue surfaces when the optical cable 16 is inserted intothe esophagus or the respiratory tract of a patient.

As shown in FIG. 2, the optical cable 16 includes 40 waveguides 18.However, the phototherapy system 10 is not limited to this configurationas the number of waveguides 18 can be different in other configurations.For example, the optical cable 16 can include one waveguide 18, or theoptical cable 16 can include any number of waveguides 18, as desired, aslong as the waveguide diameter D_(f) is small enough to fit the desirednumber of waveguides 18 within the diameter D of the optical cable 16.

With reference to FIGS. 1-5, each of the waveguides 18 include a tip 22arranged distally from the light source 14. The tips 22 are configuredto emit the light output from the light source 14 transmitting throughthe waveguides 18. The tips 22 can be configured to diffusely emit lightby shaping the tips 22, as shown in FIGS. 3 and 4, and/or by includingdiffusion optics or elements on or within to the tips 22, as shown inFIG. 5. Diffusely emitting light from the tips 22 enables thephototherapy system 10 to uniformly treat a large volume of tissue(e.g., gas exchanging lung) within a patient. Additionally, diffuselyemitting light from the tips 22 or gating illumination withend-inhalation of fresh gas reduces the irradiance (energy per unitarea) subjected to the tissue being treated within a patient, whichreduces the probability of the treated tissue overheating.

As shown in FIG. 3, in one non-limiting example, the tips 22 can definea substantially conical shape which tapers from the diameter D_(f) ofthe waveguide down to a tip diameter Dt, where D_(t) is less than D_(f).The tapering from D_(f) down to D_(t) enables the tips 22 to diffuselyemit the light from the light source 14 by emitting light radiallyaround and axially along the tips 22. As shown in FIG. 4, in anothernon-limiting example, the tips 22 can define a substantially roundshape. The rounded shape of the tips 22 enables the tips 22 to diffuselyemit light radially around the tips 22. The illustrated tips 22 of FIG.4 defines a tip diameter D_(t) approximately equal to the diameter ofthe waveguide D_(f). Alternatively, the tip diameter D_(t) may begreater than or less than the diameter of the waveguide D_(f), asdesired. It would be known by one of skill in the art that other shapes,or geometries, of the tips 22 are possible to aid in the diffusion ofthe light emitted from the tips 22.

As shown in FIG. 5, in yet another non-limiting example, the tips 22 caninclude one or more diffusing elements 24 arranged on or within the tips22. The diffusing elements 24 can be in the form of notches machinedinto the tips 22, optical lenses arranged on or within the tips 22,scattering particles arranged within the tips 22, or any other diffusingelement known in the art. Regardless of the form of the diffusingelements 24, once the light output from the light source 14 transmittingthrough the waveguides 18 contacts the diffusing elements 24, thediffusing elements 24 scatter the incident light, which then causeslight to emit diffusely and radially around the sides of the tips 22.

In still other non-limiting examples, the tips 22 may leverage beamdivergence and natural scattering through air or water to diffuselypropagate the light emitted from the tips 22.

Turning to FIG. 6, the optical cable 16 may be configured to be insertedinto an esophagus 28 of a patient 30 to position the waveguides 18within the esophagus 28. The optical cable 16 can be inserted into theesophagus 28, by a user of the phototherapy system 10, orally or throughthe nares of the patient 30. The distal end 20 of the optical cable 16,and thereby the tips 22, can be positioned at any desired location alongthe esophagus 28. In one non-limiting example, the optical cable 16 caninclude incremented distance markers that provide a user of thephototherapy system 10 an indication of how far the distal end 20 of theoptical cable 16 is inserted into the esophagus 28.

Additionally or alternatively, as shown in FIG. 7, the optical cable 16may be configured to be inserted into a trachea 32 of the patient 30 toposition the waveguides 18 within the trachea 32 and/or the bronchialtree of the patient 30. In one non-limiting example, the optical cable16 can be inserted through or along side an intubation tube.Alternatively or additionally, the optical cable 16 can be insertedorally or through the nares of the patient 30. The optical cable 16 canbe manipulated by a user of the phototherapy system 10 to position thedistal end 20 of the optical cable 16, and thereby the tips 22, at anydesired location along the trachea 32 or the bronchial tree. Forexample, as shown in FIG. 7, the distal end 20 of the optical cable 16is located within the left mainstem bronchus 34 of the patient 30.Alternatively, the distal end 20 of the optical cable 16 can bemanipulated by a user of the phototherapy system 10 to be located withinthe right mainstem bronchus 36 of the patient 30. The diameter D of theoptical cable 16 can be dimensioned to be sufficiently small such thatthe optical cable 16 can be inserted past either the right or leftmainstem bronchus into smaller airways.

Alternatively or additionally, the optical cable 16 can be configured tobe inserted through a chest tube to position the waveguides 18 in thepleural spaces surrounding the lungs 33 of the patient 30, or theoptical cable 16 can be configured to position the waveguides 18 at anylocation on or within a patient's body to provide phototherapy, asdesired.

In one non-limiting example, the waveguide diameter D_(f) of thewaveguides 18 can be sufficiently small and the material the waveguides18 are fabricated from can be sufficiently flexible to enable thewaveguides 18 to be positioned by air flowing through the respiratorytract of a patient. That is, when the optical cable 16 is insertedthrough the trachea of a patient, the waveguides 18 can be carried bythe gas flowing through the patient's respiratory tract to position thewaveguides 18 throughout the bronchial tree when the patient 30 inhales(or is ventilated with positive pressure) , as shown in FIG. 8. To aidin this process, each of the tips 22 may include a fin 26, as shown inFIG. 9. The fins 26 are configured to increase the drag force, or gasresistance, across the tips 22 to aid in displacing the waveguides 18during a forced mechanical deep inhalation or large spontaneous tidalvolume, driven by positive pressure ventilation or a voluntary deepbreath. Alternatively, the waveguides 18 can be displaced during apositive pressure deployment applied by a user of the phototherapysystem 10. Each of the fins 26 can vary in size, shape, or any otherphysical characteristic that would influence the drag force, to promotedistributing the tips 22 throughout the bronchial tree. Alternatively oradditionally, the tips 22 may be coated with an adhesive that adheres totissue and/or mucus within bronchial tree of the patient 30.

FIG. 10 shows another non-limiting example of the phototherapy system 10where the distal end 20 of the optical cable 16 is split into a firstdistal section 38 and a second distal section 40. A fraction of thewaveguides 18 protrude from the first distal section 38 and theremaining fraction of the waveguides 18 protrude from the second distalsection 40. The first distal section 38 and the second distal section 40are dimensioned such that either the first distal section 38 or thesecond distal section 40 can be received within either the left mainstembronchus 34 or the right mainstem bronchus 36 of the patient 30, whenthe optical cable 16 is inserted through the patient's trachea 32, asshown in FIG. 11. Additionally, in this non-limiting example, thewaveguides 18 can be displaced throughout the bronchial tree, forexample with the aid of the fins 26, in both lungs 33 of the patient 30,as shown in FIG. 11.

FIGS. 12 and 13 show yet another non-limiting example of thephototherapy system 10 where a balloon 44 may be attached to the distalend 20 of the optical cable 16. The balloon 44 encloses the portions ofthe waveguides 18 that protrude from the distal end 20 of the opticalcable 16. The balloon 44 is fabricated from a biocompatible materialthat is capable of efficiently transmitting the light emitted from thetips 22. The balloon 44 is in communication with a gas source 46 and/ora liquid source 48 via a fluid passageway arranged within and along theoptical cable 16. The balloon 44 is configured to be expandable betweena deflated state (FIG. 12) and an inflated state (FIG. 13). Either thegas source 46 and/or the liquid source 48 can be used to expand theballoon 44 between the deflated state (FIG. 12) and the inflated state(FIG. 13). In one non-limiting example, the gas source 46 may be apressurized supply of air or oxygen. When the optical cable 16 isinserted into the esophagus 28 of the patient 30 and the balloon 44 isin the inflated state, as shown in FIG. 14, the balloon 44 can expandand thin the walls of the esophagus 28 thereby minimizing the thicknessof the wall of the esophagus 28. This can minimize the amount of tissuethat the light emitted from the tips 22 has to penetrate while applyingphototherapy within the esophagus 28 of the patient 30.

The gas source 46 and/or the liquid source 48 can provide a coolingfluid within the balloon 44. The cooling fluid can reduce heating oftissue irradiated by the light emitted from the tips 22 of thewaveguides 18. Thus, when the cooling fluid is present within theballoon 44, the tissue receiving phototherapy can tolerate a higherpower light output from the light source 14 compared to when no coolingfluid is present within the balloon 44. Additionally or alternatively,the cooling fluid can be a low absorption fluid, such as lipid emulsionsused for feeding IV, capable of transmitting and diffusely scatteringthe light output from the light source 14.

FIG. 15 shows another non-limiting example of the phototherapy system 10where the phototherapy system 10 is integrated into a bronchoscope 50.The bronchoscope 50 includes an optical port 52 coupled to the lightsource 14, a work port 54 coupled to the optical cable 16, a suctionport 56, a viewing port 58, and one or more adjustment mechanisms 60that are mechanically coupled to the optical cable 16. The suction port56 is in communication with a suction passageway that is arranged withinand along the optical cable 16. The viewing port 58 enables a user ofthe phototherapy system 10 to view images acquired by optics arranged onthe distal end 20 of the optical cable 16. The adjustment mechanisms 60are configured to adjust the position of the distal end 20 of theoptical cable 16.

The suction port 56 can be connected to a suction device configured toproduce a vacuum throughout the suction passageway for removing fluidsamples from the trachea and/or bronchial tree of a patient. The viewingport 58 and the adjustment mechanisms 60 enable a user of thephototherapy system 10 to view and adjust the position of the distal end20 of the optical cable 16 in real time.

One non-limiting example of operation of the phototherapy system 10 willbe descried with reference to FIGS. 1-16. In operation, a user of thephototherapy system 10 can treat a patient with CO poisoning. The stepsthe user can perform to treat the patient with CO poisoning areillustrated in FIG. 16. The user of the phototherapy system 10 is,typically, a trained healthcare professional. It should be known thatthe following description of the treatment of CO poisoning using thephototherapy system 10 is one exemplary non-limiting example and, aswill be recognized by one of skill in the art, alternative methods ordifferent steps may be used.

As shown in FIG. 16, first, the waveguides 18 are positioned at step 62by the user such that the waveguides 18 directly emit light onto aportion of the patient's body (e.g., lungs or skin). Positioning thewaveguides 18 at step 62 can be accomplished by inserting the opticalcable 16 into the esophagus, trachea, bronchial tree, or pleural spaces(e.g., via a thoracotomy tube or tubes) of the patient. Alternatively,the waveguides 18 can be positioned on, within, or upon (e.g. skin) anyportion of the patient's body, as desired. In another non-limitingexample, the waveguides 18 can be positioned at step 62 to directly emitlight onto the lungs of the patient following a thoracotomy. In stillanother non-limiting example, the waveguides 18 can be positioned atstep 62 to directly emit light onto all or a portion of the patient'sskin. In this non-limiting example, the patient may be provided pureoxygen (i.e., 100% O₂) to breathe and/or the body surface (i.e., theskin) of the patient may be flushed with, or exposed to, pure oxygen.

Following the positioning of the waveguides 18 at step 62, the user thenturns on the light source 14 via the controller 12 at step 64. Once thelight source 14 is turned on at step 64, light is output from the lightsource 14 through the waveguides 18 and emitted onto the portion of thepatient's body. As described above, in one non-limiting example, thelight source 14 can be configured to output light at a wavelengthbetween 590 nm and 650 nm, which are wavelengths that are capable ofpenetrating into, or through, human tissue and being absorbed by COHb.Therefore, whether the waveguides 18 are positioned within theesophagus, trachea, bronchial tree, or pleural spaces of the patient,the light emitted from the waveguides 18 penetrates through thesurrounding tissue to reach the pulmonary vasculature of the patient.With the light source turned on at step 64, the light emitted from thelight source 14 and through the waveguides 18 reaches the pulmonaryvasculature. In the pulmonary vasculature, the emitted light is absorbedby COHb thereby photodissociating the CO from the Hb. Since the alveolarpartial pressure of oxygen in the lungs or surrounding the body can bemuch greater that the partial pressure of CO in the pulmonaryvasculature or skin vasculature, the oxygen pressure gradient drivesoxygen molecules to bind to deoxygenated Hb at a far greater rate thanCO. Thus, the CO is photodissociated from COHb into the alveolus of thepatient and exhaled during the next tidal gas exhalation.

Once the light source 14 is turned on at step 64, the controller 12determines at step 66 if a desired amount of light has been emitted. Ifso 68, the light source 14 is turned off at step 70 either automaticallyby the controller 12 or manually by the user via the controller 12. Ifnot 72, the light source 14 continues to be on until the controller 12determines at step 66 that the desired amount of light has been emitted.The desired amount of light emitted by the light source 14 can becorrelated to achieving a balance between providing enough phototherapyto lower the patient's arterial COHb levels (which can be measurednon-invasively and continuously using a digital pulse CO-oximeter(Massimo Corp.)), and preventing the surrounding tissue irradiated bythe light emitting from the waveguides 18 from overheating. The user cancontrol the pulse width, frequency, and energy output of the lightsource 14 via the controller 12 such that the power output by the lightsource 14 does not damage the irradiated tissue but still providessufficient photodissociation of COHb. Additionally, the user caninstruct the controller 12 to turn off the light source 14 after apredetermined amount of time to ensure that the desired amount of lightis emitted and the irradiated tissue is not damaged. Alternatively oradditionally, the light provided from the light source 14 can be gatedvia the controller 12 to some portion of the inspiration of fresh gas,and then turned off during exhalation to reduce tissue heating.

Once the controller 12, or the user, has turned off the light source 14at step 70, the waveguides 18 can be removed at step 74 from theesophagus, trachea, bronchial tree, pleural spaces, or other portion ofthe patient's body. Alternatively or additionally, the waveguides 18 beleft in the patient's body as the waveguides 18 can be fabricated from abiodegradable material, as described above.

Alternatively or additionally, the optical cable 16 can include aballoon 44 attached to the distal end 20 of the optical cable 16, asdescribed above. In this non-limiting configuration, once the user haspositioned the waveguides 18 at step 62 in a desired location along theesophagus of the patient, the balloon 44 can be expanded at step 76 tothe inflated state thinning the walls of the esophagus. Once the balloon44 is expanded at step 76, cooling fluid can be supplied at step 78within the balloon 44 from either the gas source 46 or the liquid source48 to cool the surrounding tissue. With the cooling fluid supplied atstep 78 inside the balloon, the light source 14 can then be turned on atstep 64 by the user via the controller 12.

Alternatively or additionally, the tips 22 of the waveguides 18 caninclude fins 26, as described above. In this non-limiting configuration,once the user has positioned the waveguides 18 at step 62 in a desiredlocation within the distal trachea or bronchial tree of the patient, thewaveguides 18 can be displaced at step 80 during inhalation or apositive pressure deployment to distribute the waveguides 18 throughoutthe trachea and/or the bronchial tree of the patient. With thewaveguides 18 displaced at step 80, the light source 14 can then beturned on at step 64 by the user via the controller 12.

Alternatively or additionally, an EKG signal of the patient and/or anairflow rate through the patient's respiratory tract can be communicatedto the controller 12, as described above. In this non-limitingconfiguration, once the light source 14 is turned on at step 64, thecontroller 12 can be configured to modulate the light source 14 at step82. That is, the controller 12 can be configured to turn on and off thelight source 14 at specific times during the cardiac cycle of thepatient based on the EKG signal, or the controller 12 can be configuredto turn on the light source 14 during inhalation and turn off the lightsource 14 during exhalation as indicated by the airflow rate through thepatient's respiratory tract or expansion of the thorax using acircumferential thoracic/abdominal belt volume sensor. In othernon-limiting examples, any physiological markers or characteristicsincluding heart rate (i.e., triggering off EKG QRS complex) can be usedor combined (e.g., EKG to gate on peak pulmonary artery blood flow andventilator phase to gate on inhalation) to trigger or gate themodulation of the light source 14 at step 82.

FIG. 17 shows another non-limiting example of a phototherapy system 100for treating or preventing CO poisoning. The phototherapy system 100includes a tube 102 having a central lumen 104. The central lumen 104 ofthe tube 102 provides communication between a liquid source 106 and abag 108. The central lumen 104 also provides communication between alight source 110 and the bag 108. The tube 102 may be fabricated from aflexible, biocompatible material, such as PVC, PTFE, PES, or any otherflexible, biocompatible material known in the art. The tube 102 isdimensioned such that a diameter D of the tube 102 is small enough toensure a patient can breathe (especially not impede exhalation) aroundthe tube 102 if inserted into the patient's esophagus. Alternatively oradditionally, the tube 102 can be configured to be inserted into one ormore chest (thoracotomy) tubes to place the bag 108 within the pleuralspaces surrounding the patient's lungs. In one non-limiting example, thetube 102 can define a diameter D smaller than at least 10 mm.

The liquid source 106 is configured to supply a flow of liquid throughthe central lumen 104 to the bag 108. The liquid source 106 can beconfigured to provide water, saline solution, a low light absorptionfluid that scatters light, such as lipid emulsions used for feeding IV,or any other biocompatible liquid known in the art. The liquid providedby the liquid source 106 can provide cooling to tissue surrounding thebag 108 and/or can be mixed with the light source 110 to fluidize anddiffusely distribute the light source 110 throughout the bag 108. Thebag 108 can be fabricated from a collapsible, biocompatible materialthat is capable of efficiently transmitting the light emitted from thelight source 110. The bag 108 and or the tube 102 can be configured suchthat the bag 108 and/or the tube 102 can fit within a patient'sesophagus, within the pleural spaces surrounding the patient's lungs, orwithin any other portion of the patient's body.

The light source 110 can be a chemiluminescent liquid, a plurality ofchemiluminescent particles, a plurality of phosphorescent particles, alaser, or a LED. It is well known in the art that the reactants of aphotochemical reaction can be chosen to produce a chemiluminescentliquid/particle that emits light at a desired wavelength. Therefore, ifthe light source 110 is a chemiluminescent liquid or particle, thechemiluminescent liquid/particles can comprise reactants that produce aphotochemical reaction that emits light at a wavelength betweenapproximately 590 nm and 650 nm. In other non-limiting examples, thechemiluminescent liquid/particles can comprise reactants that produce aphotochemical reaction that emits light at a wavelength betweenapproximately 390 nm and approximately 690 nm. In still othernon-limiting examples, the chemiluminescent liquid/particles is composedreactants that produce a photochemical reaction that emits light at anywavelength absorbed by COHb.

Typically, phosphorescent particles include a dopant ion (also commonlyreferred to as a phosphor) that is doped into a host lattice. The dopantion is excited by an outside source (e.g., light radiation) to an upperexcited state and, upon relaxation back to its ground state, the dopantion emits light at a given wavelength. Phosphorescent particles are ofparticular interest because they are typically chemically inert and canconvert absorbed excitation energy into emitted light with quantumefficiencies near one-hundred percent. It is well known in the art thatthe dopant ion, the host lattice, the crystal structure of the hostlattice, the excitation source, and the concentration of the dopant ionwithin the host lattice, among other things, can influence thewavelength of light emitted by a phosphorescent particle. Therefore, ifthe light source 110 includes phosphorescent particles, thephosphorescent particles can comprise a dopant ion and host lattice thatemit light at a wavelength between approximately 590 nm andapproximately 650 nm, when excited by an excitation source 112. In othernon-limiting examples, the phosphorescent particles can comprise adopant ion and host lattice that emit light at a wavelength betweenapproximately 390 nm and approximately 690 nm, when excited by theexcitation source. In still other non-limiting examples, thephosphorescent particles can comprise a dopant ion and host lattice thatemit light at a any wavelength absorbed by COHb, when excited by theexcitation source.

If the light source 110 includes phosphorescent particles, thephototherapy system 100 can include the excitation source 112 configuredto activate the phosphorescent particles and cause the phosphorescentparticles to emit light at the desired wavelength. The excitation source112 can be a laser, a lamp, one or more LED's, or any viable excitationsource capable of activating the phosphorescent particles.

As described above, the liquid source 106 can be configured to provide alow absorption fluid that scatters light. In this non-limiting example,the low absorption fluid can be configured to transmit and scatter lightemitted by the light source 110. The light source 110 can be a lasercoupled to a waveguide, such as an optical fiber, which is placed insidethe bag 108. The bag 108 filled with the low absorption fluid couldserve as a diffuser of the light generated by the laser and transmittedto the bag 108 within the patient's pleural spaces or any other bodycavity.

One non-limiting example of operation of the phototherapy system 100will be descried with reference to FIGS. 17 and 18. In operation, a userof the phototherapy system 100 can treat a patient with CO poisoning.The steps the user can perform to treat the patient with CO poisoningare illustrated in FIG. 18. The user of the phototherapy system 100 is,typically, a trained healthcare professional. It should be known thatfollowing description of the treatment of CO poisoning using thephototherapy system 100 is one exemplary non-limiting example and, aswill be recognized by one of skill in the art, alternative methods ordifferent steps may be used.

As shown in FIG. 18, first, the bag 108 may be positioned at step 114 bythe user such that the bag 108 is positioned within a portion of thepatient's body. As described above, the portion of the patient's bodycan include the esophagus, the pleural spaces, or any other part of thebody. Following the positioning 114 of the bag 108, the light source 110can then be fluidly communicated at step 116 into the bag 108 via thecentral lumen 104. Alternatively or additionally, the liquid from theliquid source 106 can be fluidly communicated at step 116 into the bag108 via the central lumen 104. Once the light source 110 is within thebag 108, the light output from the light source 110 transmits throughthe bag 108 and emits onto the portion of the patient's body. Asdescribed above, the light source 110 can be configured to output lightat a wavelength between 590 nm and 650 nm which are wavelengths that arecapable of penetrating into, or through, human tissue and being absorbedby COHb. Therefore, whether the bag 108 is positioned within theesophagus, or pleural spaces of the patient, the light emitted from thelight source 110 penetrates through the surrounding tissue to reach thepulmonary vasculature of the patient. When the light emitted from thelight source 110 reaches the pulmonary vasculature, the emitted light isabsorbed by COHb thereby photodissociating the CO from the Hb. Since thealveolar partial pressure of oxygen is much greater that the partialpressure of CO in the pulmonary vasculature, the oxygen pressuregradient drives oxygen molecules to bind to deoxygenated Hb at a fargreater rate than CO. Thus, the CO is photodissociated from COHb intothe alveolus of the patient and exhausted during exhalation.

The bag 108, which can be thin walled and transparent, can be leftwithin the portion of the patient's body for a predetermined amount oftime to ensure that a desired amount of phototherapy is provided and theirradiated tissue is not damaged. Once the bag 108 has been within theportion of the patient's body for the predetermined amount of time, theuser can then remove the bag 108 at step 118 from within the portion ofthe patient's body.

Alternatively or additionally, the light source 110 can includephosphorescent particles, as described above. In this non-limitingexample, before the light source 110 is fluidly communicated into thebag 108 at step 116, the light source 110 can be activated by theexcitation source 112.

It should be appreciated that, in other non-limiting examples, the bag108 may not be necessary to provide a barrier between the light source110 the portion of the patient's body. That is, in some non-limitingexamples, the light source 110 may be a non-toxic, chemiluminescentfluid that can be infused into, for example, the pleural space of thepatient to provide a better distribution of light emission from thelight source 110. Following the desired duration of phototherapyprovided by the light source 110, the light source can be removed, forexample, via suction.

FIG. 19 shows another non-limiting example of a phototherapy system 200for treating or preventing CO poisoning. The phototherapy system 200includes a light source 202 and a tube 204 having a central lumen 206.The tube 204 is configured to provide communication between the lightsource 202 and an airway 208. The illustrated airway 208 is in the formof a mask; however, in other non-limiting examples, the airway 208 maybe in the form of any device configured to provide communication to thelungs of the patient. That is, in other non-limiting examples, theairway 208 may be in the form of an endotracheal tube, nasal prongs, ora tracheostomy tube, to name a few. Alternatively or additionally, theairway 208 can be any mask, or respirator, known in the art which coversat least one of a patient's nose and mouth. For example, the airway 208can be a respirator typically worn by firemen and/or military personnel.The tube 204 may be fabricated from a flexible, biocompatible material,such as PVC, PTFE, PES, or any other flexible, biocompatible materialknown in the art. Alternatively or additionally, the tube 204 can beconnected to an endotracheal tube.

The light source 202 may comprise a plurality of phosphorescentparticles. The phosphorescent particles of the light source 202 comprisea dopant ion and host lattice that emit light at a wavelength betweenapproximately 590 nm and approximately 650 nm, when excited by anexcitation source 216. Additionally, the phosphorescent particles of thelight source 202 are chemically inert and non-toxic to human beings. Inother non-limiting examples, the phosphorescent particles can comprise adopant ion and host lattice that emit light at a wavelength betweenapproximately 390 nm and approximately 690 nm, when excited by theexcitation source 216. In still other non-limiting examples, thephosphorescent particles can comprise a dopant ion and host lattice thatemit light at a any wavelength absorbed by COHb, when excited by theexcitation source 216.

The phosphorescent particles of the light source 202 can define varyingparticle diameters such that the phosphorescent particles, when inhaledby a person, come to rest in locations throughout the trachea andbronchial tree. Additionally or alternatively, the phosphorescentparticles can be coated with an adhesive that adheres the phosphorescentparticles to mucus and/or tissue within the trachea or bronchial tree ofa person.

As shown in FIG. 19, the light source 202 is also in communication withan aerosolizing element 210 and a gas source 212. The aerosolizingelement 210 is configured to aerosolize the phosphorescent particlesthereby enabling the phosphorescent particles mix with a flow of fluidprovided by the gas source 212 and flow through the central lumen 206 ofthe tube 204 and into the airway 208. The aerosolizing element 210 mayalso configured to aerosolize a specific number of phosphorescentparticles such that a particle load inhaled by a person would not causesignificant damage to the person's lungs (biologically inert particleswhich are not bioreactive). The aerosolizing element 210 can be anebulizer, a fluidized bed, or any other viable aerosolizing deviceknown in the art. The gas source 212 can be a pressurized source of airor oxygen. The aerosol size can be engineered by size to target theportion of the lung most useful to produce CO exhalation duringpoisoning. For example, 1-2 micron particles for targeting the alveoli,5-10 micron particles to lodge in terminal bronchi, which are close tothe pulmonary arterial supply to alveoli.

A controller 214 is in communication with the aerosolizing element 210and the excitation source 216. The controller 214 is configured tocontrol when the aerosolizing element 210 aerosolizes the light source202 and when the excitation source 216 activates the light source 202.The excitation source 216 can be a laser, a lamp, one or more LED's, orany viable excitation source capable of activating the light source 202.

One non-limiting example of operation of the phototherapy system 200will be descried with reference to FIGS. 19 and 20. In operation, thephototherapy system 200 can treat a person with CO poisoning or be usedto prevent CO poisoning with a person in an atmosphere with an elevatedCO concentration. The steps for treating or preventing CO poisoningusing the phototherapy system 200 are illustrated in FIG. 20. It shouldbe known that following description of the treatment or prevention of COpoisoning using the phototherapy system 200 is one exemplarynon-limiting example and, as will be recognized by one of skill in theart, alternative methods or different steps may be used.

As shown in FIG. 20, first, the phosphorescent particles of the lightsource 202 may be activated at step 218 via the controller 214instructing the excitation source 216 to turn on. Once thephosphorescent particles of the light source 202 are is activated atstep 218, the controller 214 then instructs the aerosolizing element 210to aerosolize the phosphorescent particles at step 220. The aerosolizedphosphorescent particles are then mixed at step 222 with a fluid flowfrom the gas source 212 which enables the aerosolized phosphorescentparticles to flow into the central lumen 206 of the tube 204. Asdescribed above, the aerosolized element 210 can be configured tocontrol the particle load of the phosphorescent particles within thecentral lumen 206 such that, when inhaled by a person, the particle loadwould not cause significant damage to a person's lungs.

Once the aerosolized phosphorescent particles are mixed at step 222 withthe fluid flow from the gas source 212 and begin to flow into thecentral lumen 206, a person wearing the airway 208 could inhale theaerosolized light source 202 at step 224 causing the phosphorescentparticles of the light source 202 to scatter throughout the person'strachea and bronchial tree. As described above, the phosphorescentparticles, once activated, can be configured to output light at awavelength between 590 nm and 650 nm, which are wavelengths that arecapable of penetrating into, or through, human tissue and being absorbedby COHb. Therefore, the light emitted from the phosphorescent particlesscattered throughout the person's trachea and bronchial tract canpenetrate through the surrounding tissue to reach the pulmonaryvasculature of the person. When the light emitted from thephosphorescent particles reaches the pulmonary vasculature, the emittedlight is absorbed by COHb thereby photodissociating the CO from the Hb.Since the alveolar partial pressure of oxygen is much greater that thepartial pressure of CO in the pulmonary vasculature, the oxygen pressuregradient drives oxygen molecules to bind to deoxygenated Hb at a fargreater rate than CO. Thus, the CO is photodissociated from COHb intothe alveolus of the person and removed from the body by exhalation.

It should also be known that the light source 202, when inhaled, canreach the person's alveoli and, therefore, the thickness of tissue to bepenetrated will be very small (e.g., less than 1-5 microns). In thisnon-limiting example, the phosphorescent particles can be configured tooutput light at a wavelength between 390 nm and 750 nm.

Alternatively or additionally, the phosphorescent particles can benano-sized particles, such as lipid nanoparticles (e.g., inhaledamikacin antibiotics, or rhodamine S lipid nanoparticles), which, wheninjected, or inhaled, are configured to localize in the lungs. In thisnon-limiting example, the phosphorescent particles can be configured tooutput light at any wavelength absorbed by COHb, as no penetration oftissue would be needed.

As mentioned above the phototherapy system 200 can be used to prevent COpoisoning. This non-limiting application, can be directed towards, forexample, military personnel or firemen, who can be required to performin atmospheres with elevated CO concentrations. In one non-limitingexample, the phototherapy system 200 can be integrated into a respiratorused by military personnel or firemen. Additionally, the phototherapysystem 200 can include a measurement device, for example atranscutaneous COHb pulse oximeter, capable of continuously measuringthe arterial CO concentration in a person's blood, and the controller214 can be configured to aerosolize the light source 202 via theaerosolizing element 210 in response to measuring an elevated COconcentration in the person's blood.

EXAMPLES

The following examples set forth, in detail, ways in which thephototherapy systems described herein may be used or implemented, andwill enable one of skill in the art to more readily understand theprinciple thereof. The following examples are presented by way ofillustration and are not meant to be limiting in any way.

Mice Studies

Mice were anesthetized with an intraperitoneal (i.p.) injection ofketamine (120 mg·kg³¹ ¹) and fentanyl (0.9 mg·kg⁻¹). Following atracheotomy, rocuronium (1 mg·kg⁻¹) was injected i.p. to induce musclerelaxation. Volume-controlled ventilation was provided at a respiratoryrate of 90 breaths·min⁻¹, a tidal volume of 10 ml·kg⁻¹ and a positiveend expiratory pressure (PEEP) of 1 cm H₂O. Catheters were placed in thecarotid artery and jugular vein; then mice underwent a medianthoracotomy to expose the lungs.

Mice were poisoned by breathing 400 ppm CO in air. Inhaled and exhaledCO concentrations were measured using a CO analyzer (MSA Altair-PRO; MSASafety Inc., Pittsburgh, Pa.). In some experiments, mice were poisonedby breathing 2000 ppm CO in air and CO concentration was measured usingan infra-red CO gas analyzer (MIR2M; Altech-Environment, Geneva, Ill.).The percentage of COHb in arterial blood was sampled and measured duringand after CO poisoning and COHb half-life was calculated.

Light at 532 and 690 nm wavelength was generated by an Aura KTP laser(American Medical Systems, Minnetonka, Minn.) and a prototype laser(Syneron-Candela, Wayland, Mass.) respectively. Light at 570, 592 and628 nm wavelength was generated by Visible Fiber Lasers (VFL-P lasers,MPB Communications Inc., Montreál, Canada). The power of the lightirradiating the lungs was measured with a power meter (Thorlabs Inc.,Dachau, Germany). The light irradiance was calculated as I=Power(W)/Area (cm²). The radiant exposure was calculated as RE(J·cm⁻²)=I(W·cm⁻²)·t (sec) where RE is radiant exposure, I is irradianceand t is the time of exposure.

A 1 mm diameter optical fiber with a 1.2 cm long diffusing tip, whichemits light at 360 degrees, was placed via the oropharynx into theesophagus of anesthetized and mechanically ventilated mice. Intermittentphototherapy with light at 532 nm was tested. The power was set to 1.5 Wand light was pulsed at 1 Hz with a 200 ms pulse width.

Statistical analysis was performed using Sigma Plot 12.5 (SPPS, Inc.,Chicago, Ill.). Data were analyzed using Student's t-test and a one-wayANOVA with post hoc Bonferroni test (two-tailed). Two Way ANOVA forrepeated measurements was used to compare variables over time betweengroups. For survival analyses, Kaplan-Meier estimates were generated andcompared using the log-rank test. Statistical significance was definedas a p value of less than 0.5. All data are expressed as mean±SD unlessspecified otherwise.

To investigate whether visible light might be used to dissociate CO fromhemoglobin in vivo, a murine model of CO poisoning was developed.Anesthetized and mechanically ventilated mice were poisoned by inhaling400 parts per million (ppm) CO in air for one hour and subsequentlytreated by breathing either air or 100% O₂. The exhaled CO concentrationwas continuously monitored and the CO uptake and elimination rates weredetermined. During CO poisoning and subsequent treatment periods, COHbconcentration in arterial blood was measured sequentially and theCOHb-t_(1/2) was calculated.

The area under the curve (AUC) of exhaled CO concentration during thetreatment period represents the eliminated quantity of CO. The exhaledCO concentration during the first 15 minutes of breathing 100% O₂ wassignificantly greater than the first 15 minutes of breathing air,indicating that a larger amount of CO was eliminated during this period(AUC: 3568±242 vs. 1744±101, p<0.001), as shown in FIG. 21A. Incontrast, after approximately 20 minutes of treatment, the exhaled COconcentration was significantly higher in air-breathing mice,demonstrating the presence of a larger amount of CO remaining forelimination (AUC: 858±41 vs. 275±49, p<0.001).

At the end of the one-hour poisoning period, 28.0±0.6% (mean±SD) ofcirculating hemoglobin was saturated with CO. Treatment by ventilationwith 100% O₂ decreased COHb concentration faster than treatment with air(COHb-t_(1/2): 8.2±1.2 vs. 31.5±3.1 min, p<0.001), as shown in FIG. 21B.In this murine model, both the exhaled CO concentration and arterialCOHb levels reflect the advantage of breathing 100% O₂ over breathingair after CO poisoning.

To evaluate the effect of direct illumination of lungs on the COelimination rate, anesthetized and mechanically ventilated mice weresubjected to a median sternotomy to expose both lungs. After breathing400 ppm CO for one hour, the mice were treated by ventilation witheither air or 100% O₂, with or without phototherapy at 628 nm wavelength(λ) and 54 mW·cm⁻² irradiance. The test setup for these studies is shownin FIG. 22.

Pulmonary phototherapy added to 100% O₂ breathing induced a dramaticincrease of exhaled CO concentration during the first 5 minutes oftreatment, indicating greater CO elimination (AUC: 2763±215 vs.1904±106; p<0.001), as shown in FIG. 23A. Commencing at 8 minutes oftreatment, exhaled CO levels were significantly higher in mice treatedwith 100% O₂ alone as compared with light and 100% O₂, demonstrating thepresence of a larger amount of CO remaining to be eliminated in theformer. The reduction of blood COHb concentration during treatment with100% O₂ and phototherapy was greater than treatment with 100% O₂ alone,and the COHb-t_(1/2) was significantly shorter (3.8±0.5 vs. 8.2±1.2 min,p<0.001), as shown in FIG. 23B.

To evaluate the efficacy of phototherapy in the presence of a lowerconcentration of inspired O₂, whether lung phototherapy could increasethe CO elimination rate while mice were breathing air was tested.Phototherapy added to air breathing was associated with an increasedquantity of CO eliminated during the first 25 minutes of treatment (AUC:3451±175 vs. 2359±130, p<0.001), as shown in FIG. 23C, and COHb-t_(1/2)was significantly shorter (19.2±1.3 vs. 31.5±3.1 min, p<0.001), as shownin FIG. 23D. There was not a significant difference in systemic arterialpressure, heart rate, rectal or lung surface temperature between micetreated with or without phototherapy, as shown in FIGS. 24A, 24B, and25. These results show that after CO poisoning, direct lung phototherapyincreased the rate of CO elimination in mice breathing either 100% O₂ orair.

To test whether visible light at different wavelengths could dissociateCOHb in vivo, mice were poisoned with CO and treated with phototherapyusing light at 532, 570 (green), 592 (yellow) or 628 (red) nm. Toexclude non-specific effects of lung illumination on the CO eliminationrate, light at 690 nm (infra-red), which does not dissociate COHb invitro was also tested. Mice were anesthetized, mechanically ventilated,subjected to a midline thoracotomy and then poisoned with 400 ppm CO for5 minutes followed by 25 minutes of treatment with 100% O₂, either aloneor together with phototherapy at each chosen wavelength. The COelimination rate was determined by calculating the time necessary toeliminate 90% of the CO absorbed during the poisoning period(T_(90%)CO). Phototherapy at 532, 570, 592 or 628 nm, when added to 100%O₂ treatment, significantly decreased the T₉₀% CO when compared to 100%O₂ alone (respectively 8.7±1.2, 7.2±0.2, 8.8±2.2, 10.2±2.7 vs. 21.8±2.4min, each comparison p<0.005), as shown in FIG. 26A. In contrast,phototherapy at 690 nm did not decrease the T₉₀%CO when compared to 100%O₂ breathing alone (19.4±1.5 vs. 21.8±2.4 min, p=0.892). These resultsshow that phototherapy at wavelengths between 532 and 628 nm improves COelimination rate in CO— poisoned mice.

To investigate the relationship between the light energy and the COHbphotodissociation efficiency, mice were poisoned with CO and treatedwith 100% O₂ combined with continuous phototherapy at 628 nm usingeither a low, medium or high power (irradiance=24, 54 and 80 mW·cm⁻²).Each of these three energy levels decreased blood COHb-t_(1/2) ascompared to mice treated by breathing 100% O₂ alone (4.8±0.5, 3.8±0.5,3.1±0.2 vs. 8.2±1.2 min, each comparison p<0.001), as shown in FIG. 26B.The results show that continuous phototherapy with an irradiance as lowas 24 mW·cm⁻² effectively increased the rate of CO elimination.Moreover, the reduction in COHb-t_(1/2) obtained with phototherapy wasenhanced with the increase of the energy of incident light.

Heat produced by continuous irradiation might damage the lung. Oneapproach to reduce tissue heating is to administer the lightintermittently. To investigate the effect of intermittent phototherapyon the CO elimination rate, mice were poisoned with 400 ppm CO for 5minutes followed by 25 minutes of treatment with 100% O₂ alone or withlight at three energy levels (80,160 and 250 mW·cm⁻²) and threedifferent pulse widths (100, 500, 1000 msec) at a constant frequency of1 Hz. When using light at 80 mW·cm⁻² and with a pulse width of 100 msec,T₉₀%CO was not decreased when compared to breathing 100% O₂ alone, asshown in FIG. 26C. At each energy level, the longer the pulse thegreater was the reduction in T₉₀%CO. At each pulse width tested, T₉₀%COwas reduced when the irradiance was increased from 80 to 160 mW·cm⁻².There was no further reduction when the irradiance was increased to 250mW·cm⁻². These results show that intermittent phototherapy can alsoimprove the rate of CO elimination, although the effect is less thancontinuous phototherapy.

To evaluate the combined effects of pulse width and light irradiance onthe CO elimination rate, the radiant exposure for each treatment wascalculated. The relationship between the CO elimination rate and theradiant exposure is described by a three parameter exponential decaycurve (R²=0.93, p<0.0001) shown in FIG. 26D. As shown in FIG. 26D, whenthe radiant exposure is greater than 0.8 J·cm⁻², a plateau is reached,and a further increase of either power or pulse duration does notincrease the CO elimination rate.

To test whether phototherapy might prevent CO poisoning during COexposure, anesthetized and mechanically ventilated mice were exposed to400 ppm CO in air for one hour with or without simultaneous direct lungphototherapy at 628 nm. The exhaled CO concentration was significantlygreater in mice treated with phototherapy during the poisoning, as shownin FIG. 27A, and the amount of CO absorbed by these mice wassignificantly less than control mice (0.134±0.005 vs. 0.189±0.11umol·g⁻1, p<0.001), as shown in FIG. 27B. In mice receiving phototherapyduring CO exposure, arterial blood COHb levels at 20, 40 and 60 minuteswere significantly lower than in controls (13.4±1.1 vs. 16.5±1.9,16.8±1.1 vs. 24.2±1.2, 18.4±0.6 vs. 28.0±0.6% respectively, p<0.001), asshown in FIG. 27C. These results show that direct lung illuminationduring ongoing CO exposure is associated with reduced CO absorption andlower arterial COHb levels.

Because phototherapy during CO poisoning decreased the amount ofabsorbed CO, whether phototherapy might improve the survival rate ofmice breathing high levels of CO was explored. Mice breathed 2000 ppm COin air for one hour, with or without simultaneous direct lungphototherapy at 532 nm. Without phototherapy, all of the mice diedwithin 30 minutes of CO exposure. In contrast, 5 of 6 mice breathing COand treated with phototherapy survived for 60 minutes, as shown in FIG.28A. During CO poisoning, the blood COHb levels in phototherapy-treatedmice were significantly less than in control mice (34.1±3.5 vs.49.9±1.9% at 10 min and 38.5±4.0 vs. 62.0±0.9% at 20 min, respectively,p<0.001), as shown in FIG. 28B. In the first 15 minutes of CO exposure,the systolic arterial pressure decreased and the heart rate transientlyincreased in both groups, as shown in FIGS. 28C and 28D. Thereafterblood pressure and heart rate dramatically decreased in untreated micewhile they remained constant in phototherapy-treated mice. During thestudy period, blood lactate levels were significantly lower inphototherapy-treated mice as compared with untreated mice (3.4±1.0 vs.4.6±1.0 mmol·L⁻¹ at 10 min, p=0.5 and 3.7±1.0 vs. 11.0±1.5 mmol·L⁻¹ at20 min, p<0.001), as shown in FIG. 28E. These results show that directlung phototherapy improves the survival rate of mice undergoing COpoisoning. The reduced degree of CO intoxication was associated withlower blood COHb and lactate levels.

To evaluate the possibility of delivering phototherapy to murine lungswithout a thoracotomy, the effect of delivering light to the lungs viaan optical fiber with a diffusing tip placed via the oropharynx into theesophagus was explored. To optimize the position of the esophagealoptical fiber in relation to the lungs, a CT scan of a living,anesthetized and mechanically ventilated 25 g mouse was captured, asshown in FIG. 29A. The optimal location of the fiber to irradiate thelower portion of the lungs was reached when the end of the fiber was 3.9cm from the mandibular incisors.

After breathing 400 ppm CO for one hour, mice were treated byventilation with 100% O₂ alone or combined with trans-esophagealphototherapy of the lung. The quantity of CO eliminated during the first5 minutes of treatment was significantly greater in mice treated withesophageal phototherapy (AUC: 2246±85 vs. 2030±83 respectively,p=0.001), as shown in FIG. 29B, and COHb-t_(1/2) was significantlyshorter with phototherapy than in mice breathing 100% O₂ alone (5.7±0.3vs. 6.8±0.3 min, p<0.001), as shown in FIG. 29C. These resultsdemonstrate that esophageal phototherapy increased the rate of COelimination when compared to 100% O₂ breathing alone.

Rat Studies

To further test the efficacy of the phototherapy systems and methodsdescribed herein, pulmonary phototherapy was tested in rats, an animalweighing approximately 18 times more than mice. All animal experimentswere approved by the Subcommittee on Research Animal Care of theMassachusetts General Hospital, Boston, Mass. 49 male Sprague Dawleyrats (Charles River Laboratories, Wilmington, Mass., USA) weighing454±69 g (mean ±SD) were tested. Rats were anesthetized withintraperitoneal (i.p.) ketamine (100 mg·kg⁻¹) and fentanyl (50mcg·kg⁻¹). Following a tracheostomy, rocuronium (1 mg·kg⁻¹) was injectedi.p. to induce muscle relaxation and rats were mechanically ventilated(Inspira; Harvard Apparatus, Holliston, Mass., USA). Volume-controlledventilation was provided at a respiratory rate of 40 breaths·min⁻¹, atidal volume of 10 ml·kg⁻¹, positive end expiratory pressure (PEEP) of 2cm H₂O and inspired oxygen fraction (FIO₂) of 0.21. Catheters wereplaced in the carotid artery and jugular vein. Arterial blood pressure,heart rate, body temperature and peak airway pressure were continuouslymonitored. Continuous i.v. anesthesia and muscle relaxation wereprovided with fentanyl (1.2-2.4 mcg·kg⁻¹·j⁻¹), ketamine (10-20mg·kg⁻¹·h⁻¹) and rocuronium (2-4 mg·kg·⁻¹·h⁻¹). Ringer's Lactate wasinfused at a rate of 8-12 ml·kg⁻¹·h⁻.

To test whether direct phototherapy could increase the rate of COelimination in an animal that is 18 times heavier than a mouse, a modelof CO poisoning in rats was developed. Anesthetized and mechanicallyventilated rats were poisoned for 90 minutes breathing 500 ppm CO inair, and then treated with either air or 100% oxygen. As observed duringthe poisoning period in mice (FIGS. 23A and 23B), the exhaled COconcentration slowly increased, indicating that a large amount of CO wasabsorbed by the rat at the beginning of poisoning, as shown in FIG. 30A.Over time, smaller amounts CO were absorbed as the circulatinghemoglobin became progressively saturated with CO. After the poisoningperiod, rats were treated by breathing either 100% oxygen or room air ata constant minute ventilation. During the first 30 minutes of treatmentbreathing 100% oxygen, the exhaled CO concentration was significantlygreater than that of rats breathing air, and the calculated quantity ofCO eliminated during this time was significantly greater (3.8±0.1 vs.2.0±0.3 ml·kg−1, p<0.001). In parallel, blood COHb decreased faster, andCOHb-t_(1/2) was shorter when rats breathed 100% oxygen (100% oxygen vs.room air: 12.0±0.5 vs. 53.5±5.1 min, p<0.001), as shown in FIG. 30B.These results show that the rat model of CO poisoning is suitable forstudying the effects of various treatments on the rate of COelimination.

To directly illuminate the lungs, anesthetized rats underwent a medianthoracotomy. Light at 532 nm wavelength was generated by an Aura KTPlaser (American Medical Systems, Minnetonka, Minn., USA) and deliveredto both lungs via an optical fiber. The tip of the fiber was placed at10 cm distance from the lung's surface, so that the area of the lightbeam was sufficiently wide to illuminate the anterior surface of eachlung. The power of the laser was set to illuminate the lungs with anirradiance of 54 mW·cm⁻².

To test whether phototherapy increases the CO elimination rate, ratswere poisoned by breathing CO at 500 ppm for 90 minutes in air and thentreated by breathing either air or 100% oxygen with or without addingdirect lung phototherapy. As shown in FIG. 31A, when animals weretreated with either 100% oxygen or room air, the addition of pulmonaryphototherapy significantly increased the rate of CO elimination, asdemonstrated by a greater amount of exhaled CO measured during the first10 minutes of treatment (100% oxygen vs. 100% oxygen plus phototherapy:2.2±0.1 vs. 2.7±0.4 ml·kg−1, p<0.5; air vs. air plus phototherapy:0.9±0.1 vs. 1.2±0.1 ml·kg−1, p=0.1). Concomitantly, as shown in FIG.31B, there was a more rapid reduction of blood COHb levels(COHb-t_(1/2): 100% oxygen vs. 100% oxygen plus phototherapy: 12.0±0.5vs. 7.4±1.0 min, p<0.001; air vs. air plus phototherapy: 53.5±5.1 vs.38.4±4.6 min, p=0.004). These results demonstrate that direct pulmonaryphototherapy increases the rate of CO elimination in rats breathingeither air or 100% oxygen.

To study whether the more rapid reduction of COHb levels observed withphototherapy could have a salutary effect on oxygen delivery andmetabolism after severe CO poisoning, rats were exposed to breathing2000 ppm CO in air until their blood lactate levels reached aconcentration of 7 mmol/L or higher. All animals reached the targetlactate concentration within 50 minutes of breathing CO; animals werethen treated by breathing air with or without phototherapy. As shown inFIGS. 32A and 32B, during the poisoning period the mean arterialpressure and the heart rate decreased from 107±3 to 56±1 mmHg and from350±15 to 293±12 beats/min respectively (mean±SEM). Mean arterialpressure and heart rate during treatment were not different inphototherapy-treated rats as compared with rats breathing air alone.Importantly, the COHb level decreased faster during treatment withphototherapy. The blood lactate concentration was also lower after 20,40 and 60 minutes of treatment with phototherapy and room air comparedto room air alone (20 minutes: 3.7±0.5 vs. 5.8±0.4 mmol/L, p=0.1; 40minutes: 1.6±0.2 vs. 4.1±0.9 mmol/L, p=0.009; 60 minutes: 1.0±0.1 vs.3.2±1.0 mmol/L, p=0.2), as shown in FIGS. 32C and 32D. These resultsshow that CO-poisoned rats breathing air and treated with pulmonaryphototherapy have improved lactate clearance.

To study whether the combination of isocapnic hyperventilation andpulmonary phototherapy would augment the rate of CO elimination,anesthetized and mechanically ventilated rats were poisoned by breathing500 ppm CO in air for 90 minutes and then treated with isocapnichyperventilation with or without direct lung phototherapy at 54 mW·cm−2.Despite a slightly lower inspired oxygen concentration (approximately95% vs. 100%) due to the addition of 5% CO2 to maintain a constantarterial PaCO2 and avoid hypocapnia, animals treated with isocapnichyperventilation had a more rapid decrease of blood COHb levels comparedto animals treated with 100% oxygen with a normal minute ventilationrate (COHb-t_(1/2): 7.1±0.4 vs. 12.0±0.5 min, p<0.001). The combinationof direct pulmonary phototherapy and isocapnic hyperventilationincreased the rate of CO elimination as compared with isocapnichyperventilation alone, as demonstrated by a larger amount of COeliminated during the first ten minutes of treatment (isocapnichyperventilation plus phototherapy vs. isocapnic hyperventilation alone:6.1±0.6 vs. 4.2±0.3 ml·kg−1, p=0.001), as shown in FIG. 33A. Also, adecreased COHb-t_(1/2) (5.2±0.5 vs. 7.1±0.4 min, p=0.002) was observed,as shown in FIG. 33B. These results show that increased minuteventilation increases the rate of CO elimination in rats. Moreover,combining pulmonary phototherapy and isocapnic hyperventilation with 95%oxygen can further increase the rate of CO elimination.

Intrapleural phototherapy was tested using two optical fibers with 3.5cm long diffusing tips emitting light in all directions were placed inthe right and left pleural spaces of rats. In anesthetized, mechanicallyventilated supine rats, 1.5 cm long incisions were made in the abdominalwall in the right and left hypochondriac regions. After exposing theabdominal cavity and the lower surface of the diaphragm, two 2 mmincisions were made in the diaphragm and one optical fiber was placed inboth the right and left pleural spaces. To irradiate each lung withsufficient power, the right fiber was connected to the Aura KTP laserand the left fiber was connected to a frequency-doubled Nd:YAG laser(IRIDEX Corp., Mountain View, Calif.), both lasers generating light at532 nm. The power of the light emitted by the diffusing optical fiberswas 570 (right pleural space) and 450 (left pleural space) mW.

To treat CO poisoning with direct lung irradiation, the intrapleuralapproach to light delivery to the lungs was employed. After 90 minutesof poisoning with 500 ppm CO, rats were treated with 100% oxygen with orwithout intrapleural phototherapy. Compared with rats treated with 100%oxygen alone, intrapleural phototherapy combined with 100% oxygen wasassociated with a greater quantity of CO elimination during the firstten minutes of treatment (2.4±0.2 vs. 2.1±0.1 ml·kg−1, p=0.009), asshown in FIG. 34A, and a shorter COHb-t_(1/2) (9.8±0.5 vs. 11.7±0.3 min,p<0.001), as shown in FIG. 34B. These results demonstrate thatintrapleural phototherapy can increase the rate of CO elimination in aCO poisoned rat breathing 100% oxygen.

Whether light generated by chemiluminescence would dissociate CO in vivoand increase the rate of CO elimination was tested. The light spectrumgenerated by the chemiluminescence reaction was measured with aspectrophotometer, showing a peak wavelength of 517 nm and a centralwavelength of 532 nm (bandwidth (90%)=110 nm), as shown in FIG. 35. Inanesthetized rats at thoracotomy, a custom-fabricated clear polyethylenesack was placed around each lung. Each sack had a small catheterallowing the injection of chemiluminescent fluid into the sack. After 90minutes of CO poisoning, the luminescent fluid was injected into thepolyethylene bags while the animal breathed 100% oxygen. In controlanimals, the polyethylene bags were filled with an equal volume ofsaline.

To test the efficacy of the chemiluminescence approach, CO eliminationrate in CO-poisoned rats was measured. After 90 minutes of CO poisoningby breathing 500 ppm CO in air, rats were treated with 100% oxygen withor without light emitted by a chemiluminescent fluid injected into thetwo clear sacks. The amount of CO exhaled during the first ten minutesof treatment was greater in rats treated with 100% oxygen andchemiluminescence-generated phototherapy as compared to rats breathing100% oxygen alone (2.4±0.1 vs. 2.1±0.1 ml·kg−1, p=0.018), as shown inFIG. 36A, and the COHb-t_(1/2) was significantly shorter (10.1±0.6 vs.11.5±0.3 min, p=0.11), as shown in FIG. 36B. These results show thatproviding green light generated by a chemiluminescent reaction in bothpleural spaces can increase the rate of CO elimination, suggesting thatprotected chemiluminescent light sources might be used to irradiate thelungs.

Thus, while the invention has been described above in connection withparticular embodiments and examples, the invention is not necessarily solimited, and that numerous other embodiments, examples, uses,modifications and departures from the embodiments, examples and uses areintended to be encompassed by the claims attached hereto. The entiredisclosure of each patent and publication cited herein is incorporatedby reference, as if each such patent or publication were individuallyincorporated by reference herein.

We claim:
 1. A phototherapy system for treating or controlling an amountof carbon monoxide poisoning in a patient, comprising: a light source incommunication with an aerosolizing element; and a tube configured toprovide communication between the light source and an airway, the airwayconfigured to provide communication to at least one of a nose and amouth of the patient, wherein the aerosolizing element is configured toaerosolize the light source to deliver the light source to the patientby ventilation of gas through the airway.
 2. The phototherapy system ofclaim 1, wherein the light source is configured to emit light at awavelength between approximately 390 nanometers and 750 nanometers. 3.The phototherapy system of claim 1, wherein the light source is aplurality of phosphorescent particles.
 4. The phototherapy system ofclaim 3, wherein the aerosolizing element is configured to aerosolize aspecific number of phosphorescent particles to achieve a predetermined aparticle load to be inhaled by the patient.
 5. The phototherapy systemof claim 3, wherein the phosphorescent particles define varyingdiameters such that, when inhaled, the phosphorescent particles arelocated throughout a trachea and a bronchial tract of the patient. 6.The phototherapy system of claim 3, wherein the phosphorescent particlesare chemically inert and non-toxic to humans.
 7. The phototherapy systemof claim 3, further comprising an excitation source configured toactivate the phosphorescent particles.
 8. The phototherapy system ofclaim 7, wherein the excitation source is at least one of a laser, alamp, and one or more light-emitting-diodes.
 9. The phototherapy systemof claim 7, further comprising a controller in communication with theexcitation source and the aerosolizing element.
 10. The phototherapysystem of claim 1, further comprising a gas source in communication withthe light source.
 11. The phototherapy system of claim 10, wherein thegas source is a pressurized supply or air or oxygen.
 12. The phototherapy system of claim 1, wherein the airway comprises at least one ofa mask, a respirator, nasal prongs, an endotracheal tube, and atracheostomy tube.